Finite element model-based evaluation of tissue stress variations to fabricate corrective orthosis in feet with neutral subtalar joint.

BACKGROUND: The subtalar joint position during static stance is a crucial determinant of the peak plantar pressures and forms ideal reference point for any intervention in foot-related problems for leprosy-affected patients. OBJECTIVES: The study pursued the hypothesis through a three-dimensional model that stress will be minimal in the distal joints of the foot when the subtalar joint is in neutral static stance position. STUDY DESIGN: Finite element model. METHODS: The computed tomography images of the feet for five patients suffering from Hansen's disease having no muscle weakness and joint restriction were acquired. The gray intensities corresponding to the bones of the foot from the computed tomography images were three-dimensionally reconstructed. The three-dimensional model of the human foot, incorporating the realistic geometry, and the material properties of the hard tissues were then analyzed using a finite element solver for the stress distribution on bones of the foot. RESULTS: The results demonstrate that the position of the calcaneum in the static stance position does contribute to the varying stress in the foot. CONCLUSION: The stresses in the bones of the foot are minimal while the subtalar is in neutral position; this position will be suitable for foot orthotic fabrication. Clinical relevance The clinicians, therapists, and podiatrists having less engineering skills can quickly assess the patient and get optimal results on the stress associated with the joints of the foot.

Has percutaneous aortic valve replacement taken center stage in the treatment of aortic valve disease?

Modern biomedical advances have propelled percutaneous valve replacement into an effective and powerful therapy for many heart valve diseases, especially aortic valve stenosis. Experiences so far suggest that outcomes for new percutaneous valve replacement surgery compare favorably with that of traditional valve surgery in selected patients with severe symptomatic aortic stenosis. The inception of percutaneous aortic valve replacement (PAVR) began in 1992 when the potential for treating valve diseases was demonstrated through a modern technique of endoluminal deployment of a catheter-mounted crimped stented heart valve in an animal model. The first successful demonstration of such novel technique of surgical replacement of a heart valve was performed in 2002, when valve implantation in a patient with aortic stenosis was reported. Despite initial stumbles and a perception of being an uphill task, PAVR has emerged as one of the breakthroughs in surgical procedures. More than 1500 citations were found in PubMed, half of which were available after 2011. This is primarily because more than 50,000 procedures are being performed in more than 40 countries worldwide, with encouraging outcomes, and several stented valves have been launched in the market. This review provides a detailed analysis of the current state of the art of PAVR. Moreover, a competitive landscape of various devices available in the market and their design considerations, biomaterial selections, and overall hemodynamic performance are presented.

Self-expanding aortic valve stent-material optimization.

Vascular support structures are important devices for treating valve stenosis. Large population of patients is treated for valvular disease and the principal mode of treatment is the use of percutaneous valvuloplasty. Stent devices are proving to be an improved technology in minimal invasive cardiac surgery. This technology now accounts for 20% of treatments in Europe. This new technology provides highly effective results at minimal cost and short duration of hospitalization. During the development process, a number of specific designs and materials have come and gone, and a few have remained. Many design changes were successful, and many were not. This paper discusses the physical behavior of a hooked percutaneous aortic valve stent design using a finite element analysis. Specifically, the effects of crimping was simulated and analyzed for two types of realistic but different Nitinol materials (NITI-1 and NITI-2). The results show that both NITI-1 and NITI-2 had good crimping performance. The analysis performed in this paper may aid in understanding the stent's displacement ranges when subjected to physiological pressures exerted by the heart and cardiac blood flow during abnormal cardiovascular conditions. It may also help to evaluate the suitability of a Nitinol for fabrication purposes.

Free Radical Scavenging, Cytotoxic and Hemolytic Activities from Leaves of Acacia nilotica (L.) Wild. ex. Delile subsp. indica (Benth.) Brenan.

Dietary intake of phytochemicals having antioxidant activity is associated with a lower risk of mortality from many diseases. Therefore, the aim of this study was to determine the free radical scavenging, cytotoxic and hemolytic activities of leaves of Acacia nilotica by using various methods. The results of the present study revealed that ethanol extract was the most effective and IC(50) value was found to be 53.6 µg mL(-1) for Vero cell lines and 28.9 µg mL(-1) for Hela cell lines in cytotoxicity assays. The zone of color retention was 14.2 mm in ß-carotene bleaching assay, which was as significant as positive control, butylated hydroxy toluene. None of the tested extracts possessed any hemolytic activity against rat and human erythrocytes revealing their cytotoxic mechanism and non-toxicity. Thus, only the ethanol extract could be considered as a potential source of anticancer and antioxidant compounds. Further phytochemical studies will be performed for specification of the biologically active principles.

Novel approach for designing a low weight hip implant used in total hip arthroplasty adopting skeletal design techniques.

Aseptic loosening is the major cause of failure of hip implants after total hip arthroplasty. Stress shielding of the femur is known to be the principal factor involved in the aseptic loosening of hip implants. Solid stems are found to have a greater rigidity; therefore, they transfer less load proximally, which results in greater stress shielding of the proximal femur. A stem of low stiffness alone would not suffice in achieving a reduced or optimal stress shielding. The femoral stem of the light weight hip implant has a skeletal design with a hexagonal base and neck cross-section. This novel design would ameliorate the implant fixation, aid in optimal rigidity, enhance the medullary revascularization, and offer better mobility to the patient.

Therapeutic Potential of Polar and Non-Polar Extracts of Cyanthillium cinereum In Vitro.

Cyanthillium cinereum (Less.) H. Rob. (Asteraceae) has been traditionally known for its medicinal properties, all aspects of which are yet to be exploited. This study was aimed at investigating the therapeutic potential of polar (methanolic and aqueous) and nonpolar (hexane and chloroform) crude extracts of the whole plant. Several parameters including free-radical (DPPH(•), ABTS(•+), H(2)O(2) and (•)OH) scavenging, reducing power, protection of DNA against oxidative damage, cytotoxicity, inhibition of oxidative hemolysis in erythrocytes, total phenolic content and inhibition of lipid peroxidation were examined. All the free-radical generating assay models demonstrated positive scavenging efficiency with differential but considerable magnitudes for the four extracts. However, only the hexane extract showed significant H(2)O(2) scavenging effect. Lipid peroxidation was estimated by thiobarbituric acid-malondialdehyde (MDA) reaction, and a high degree of inhibition was shown by all the extracts. Reducing power of the polar extracts was higher than the non-polar ones. All extracts showed a concentration-dependent increase in phenolic contents. Oxidative damage to erythrocytes was hindered by all extracts in diverse degrees. XTT assay showed that all extracts have mild cytotoxic property. The aqueous extract evidently demonstrated protective effect on pBR322 plasmid DNA against oxidative breakdown. These results suggested the potential of C. cinereum as medicine against free-radical-associated oxidative damage and related degenerative diseases involving metabolic stress, genotoxicity and cytotoxicity.

Antioxidant Activity of Lawsonia inermis Extracts Inhibits Chromium(VI)-Induced Cellular and DNA Toxicity.

Hexavalent chromium Cr(VI) is a very strong oxidant which consequently causes high cytotoxicity through oxidative stress. Prevention of Cr(VI)-induced cellular damage has been sought in this study in aqueous and methanolic extracts of Lawsonia inermis Linn. (Lythraceae), commonly known as Henna. The extracts showed significant (P < .05) potential in scavenging free radicals (DPPH(•) and ABTS(•+)) and Fe(3+), and in inhibiting lipid peroxidation. DNA damage caused by exposure of pBR322 to Cr(VI)-UV is markedly inhibited by both extracts in varying degrees. A distinct decline in Cr(VI)-induced cytotoxicity was noticed in MDA-MB-435S (human breast carcinoma) cells with an increase in dosage of both extracts individually. Furthermore, both extracts proved to contain a high content of phenolic compounds which were found to have a strong and significant (P < .05) positive correlation to the radical scavenging potential, lipid peroxidation inhibition capacity and cyto-protective efficiency against Cr(VI)-induced oxidative cellular damage. HPLC analysis identified some of the major phenolic compounds in both extracts, which might be responsible for the antioxidant potential and the properties of DNA and cyto-protection. This study contributes to the search for natural resources that might yield potent therapeutic drugs against Cr(VI)-induced oxidative cell damage.

Free radical scavenging, cytotoxic, and hemolytic activities of an active antioxidant compound ethyl gallate from leaves of Acacia nilotica (L.) Wild. Ex. Delile subsp. indica (Benth.) Brenan.

UNLABELLED: In the present study, free radical scavenging, cytotoxic, and hemolytic activities of the polyphenolic compound ethyl gallate isolated from ethanol extract of Acacia nilotica Wild. Ex. Del. leaves were determined. The free radical-scavenging activities of the ethyl gallate were demonstrated in several in vitro assays in order to evaluate the possible antioxidant mechanism. The results revealed ethyl gallate as hydrogen donor, metal chelator, and free radical scavenger. Ethyl gallate was effective in scavenging 1,1-Diphenyl-2-picrylhydrazyl (DPPH) radicals and the IC50 value was lower than all the positive controls used in this study. Deoxyribose degradation assay revealed that ethyl gallate had more iron-chelating ability than the direct hydroxyl radical-scavenging ability. The results of the cytotoxic study revealed that the compound was moderately active and IC50 value was found to be >100 µg/mL for Vero cell lines and 72 µg/mL for Hela cell lines. The compound possessed no hemolytic activity against rat and human erythrocytes revealing its cytotoxic mechanism and nontoxicity. The results from this work will provide an important information for the food and pharmacological industries with respect to the use of the compound as an antioxidant and a health-related drug. PRACTICAL APPLICATION: Antioxidant from plant sources is safe to use, as compared to synthetic products. It also can be used as a supplement to alleviate most of the diseases because of its free radical-scavenging activity.

Stent biomaterial and design selection using finite element analysis for percutaneous aortic valve replacement.

Vascular support structures are important devices for treating valve stenosis. Large populations of patients are treated for valvular disease and the principal mode of treatment is the use of percutaneous valvuloplasty. Stent devices are proving to be imperative in minimally invasive cardiac surgery. This new technology provides highly effective results at minimal cost and short duration of hospitalization. This article discusses the finite element analysis (FEA) of various percutaneous aortic valve stent designs. The stent designs were modeled and subjected to FEA. Analysis was done on four models using three biomaterials, with loads ranging from 10,665.8 N/m(2) to 26,664 N/m(2). These pressures were selected as they are equivalent to human blood pressure, which ranges from 80 mm Hg to 200 mm Hg. They were also selected to understand the mechanical behavior of different stent designs under such high pressures. Four stent models were generated and their physical, mechanical, and behavioral properties were studied. FEA and simulation of these models encouraged the designer to select the geometry and the biomaterial suitable for performance during and after implantation. The analysis performed in this article may aid in understanding the stents' performance ranges when subjected to the physiological pressures exerted by the heart and cardiac blood flow during abnormal cardiovascular conditions. It may also help in finding the best design and the biomaterial that would be suitable under such conditions.

Cytochrome P450 reductase: a harbinger of diffusible reduced oxygen species.

The bi-enzymatic system of cytochrome P450 (CYP, a hemoprotein) and cytochrome P450 reductase (CPR, a diflavoenzyme) mediate the redox metabolism of diverse indigenous and xenobiotic molecules in various cellular and organ systems, using oxygen and NADPH. Curiously, when a 1:1 ratio is seen to be optimal for metabolism, the ubiquitous CYP:CPR distribution ratio is 10 to 100:1 or higher. Further, the NADPH equivalents consumed in these in vitro or in situ assemblies usually far exceeded the amount of substrate metabolized. We aimed to find the rationale to explain for these two oddities. We report here that CPR is capable of activating molecular oxygen on its own merit, generating diffusible reduced oxygen species (DROS). Also, in the first instance for a flavoprotein, CPR is shown to deplete peroxide via diffusible radical mediated process, thereby leading to the formation of water (but without significant evolution of oxygen). We also quantitatively demonstrate that the rate of oxygen activation and peroxide depletion by CPR accounts for the major reactivity in the CYP+CPR mixture. We show unambiguously that CPR is able to regulate the concentration of diffusible reduced oxygen species in the reaction milieu. These findings point out that CPR mediated processes are bound to be energetically 'wasteful' and potentially 'hazardous' owing to the unavoidable nature of the CPR to generate and deplete DROS. Hence, we can understand that CPR is distributed at low densities in cells. Some of the activities that were primarily attributed to the heme-center of CYP are now established to be a facet of the flavins of CPR. The current approach of modeling drugs to minimize "uncoupling" on the basis of erstwhile hypothesis stands questionable, considering the ideas brought forth in this work.

Kinetics, equilibrium and thermodynamic studies on biosorption of Ag(I) from aqueous solution by macrofungus Pleurotus platypus.

Reports are available on silver binding capacity of some microorganisms. However, reports on the equilibrium studies on biosorption of silver by macrofungi are seldom known. The present study was carried out in a batch system using dead biomass of macrofungus Pleurotus platypus for the sorption of Ag(I). P. platypus exhibited the highest silver uptake of 46.7 mg g(-1) of biomass at pH 6.0 in the presence of 200 mg L(-1) Ag(I) at 20°C. Kinetic studies based on fractional power, zero order, first order, pseudo-first order, Elovich, second order and pseudo-second order rate expressions have been carried out. The results showed a very good compliance with the pseudo-first order model. The experimental data were analyzed using two parameter isotherms (Langmuir, Freundlich, Dubinin-Radushkevich, Temkin and Halsey), three parameter isotherms (Redlich-Peterson, Sips, Khan, Koble-Corrigan, Hill, Toth, Radke-Prausmitz, Jossens, Langmuir-Freundlich), four parameter isotherms (Weber-van Vliet, Fritz-Schlunder, Baudu) and five parameter isotherm (Fritz-Schlunder). Thermodynamic parameters of the biosorption (ΔG, ΔH and ΔS) were also determined. The present study confirmed that macrofungus P. platypus may be used as a cost effective efficient biosorbent for the removal of Ag(I) ions from aqueous solution.

Three-dimensional computer-aided design-based geometric modeling of a new trileaflet aortic valve.

Our objective was to design a new trileaflet aortic valve using computer-aided design (CAD). Quantification of aortic valve geometries is essential in understanding normal and pathological valvular function and eventually in the design of valves. We have designed a new tissue valve model to investigate its suitability in aortic valve replacement. Steps involved in three-dimensional CAD-based geometric modeling of a trileaflet aortic valve and the effects of different component dimensions on the mechanical behavior of valve are presented in this article. Conceptual designing of individual components was used to build the total geometric model. A new geometric model of a trileaflet aortic valve was designed. This may be of great interest to designers of new prosthetic heart valve models, as well as to surgeons involved in valve-sparing surgery.

Explaining the atypical reaction profiles of heme enzymes with a novel mechanistic hypothesis and kinetic treatment.

Many heme enzymes show remarkable versatility and atypical kinetics. The fungal extracellular enzyme chloroperoxidase (CPO) characterizes a variety of one and two electron redox reactions in the presence of hydroperoxides. A structural counterpart, found in mammalian microsomal cytochrome P450 (CYP), uses molecular oxygen plus NADPH for the oxidative metabolism (predominantly hydroxylation) of substrate in conjunction with a redox partner enzyme, cytochrome P450 reductase. In this study, we employ the two above-mentioned heme-thiolate proteins to probe the reaction kinetics and mechanism of heme enzymes. Hitherto, a substrate inhibition model based upon non-productive binding of substrate (two-site model) was used to account for the inhibition of reaction at higher substrate concentrations for the CYP reaction systems. Herein, the observation of substrate inhibition is shown for both peroxide and final substrate in CPO catalyzed peroxidations. Further, analogy is drawn in the "steady state kinetics" of CPO and CYP reaction systems. New experimental observations and analyses indicate that a scheme of competing reactions (involving primary product with enzyme or other reaction components/intermediates) is relevant in such complex reaction mixtures. The presence of non-selective reactive intermediate(s) affords alternate reaction routes at various substrate/product concentrations, thereby leading to a lowered detectable concentration of "the product of interest" in the reaction milieu. Occam's razor favors the new hypothesis. With the new hypothesis as foundation, a new biphasic treatment to analyze the kinetics is put forth. We also introduce a key concept of "substrate concentration at maximum observed rate". The new treatment affords a more acceptable fit for observable experimental kinetic data of heme redox enzymes.

Evolution, homology conservation, and identification of unique sequence signatures in GH19 family chitinases.

The discovery of GH (Glycoside Hydrolase) 19 chitinases in Streptomyces sp. raises the possibility of the presence of these proteins in other bacterial species, since they were initially thought to be confined to higher plants. The present study mainly concentrates on the phylogenetic distribution and homology conservation in GH19 family chitinases. Extensive database searches are performed to identify the presence of GH19 family chitinases in the three major super kingdoms of life. Multiple sequence alignment of all the identified GH19 chitinase family members resulted in the identification of globally conserved residues. We further identified conserved sequence motifs across the major sub groups within the family. Estimation of evolutionary distance between the various bacterial and plant chitinases are carried out to better understand the pattern of evolution. Our study also supports the horizontal gene transfer theory, which states that GH19 chitinase genes are transferred from higher plants to bacteria. Further, the present study sheds light on the phylogenetic distribution and identifies unique sequence signatures that define GH19 chitinase family of proteins. The identified motifs could be used as markers to delineate uncharacterized GH19 family chitinases. The estimation of evolutionary distance between chitinase identified in plants and bacteria shows that the flowering plants are more related to chitinase in actinobacteria than that of identified in purple bacteria. We propose a model to elucidate the natural history of GH19 family chitinases.

Effects of design parameters on the radial force of percutaneous aortic valve stents.

Valve stents are small cylindrical structures introduced in stenosed valves to replace them and restore blood flow. High radial force has become an essential feature of these stents. The primary aim of this investigation was to investigate the effects of varying stent "design parameters" on its radial force by using the finite element method (FEM). The improved model design was carried out to meet the functional and surgical requirements. The finite element model to evaluate radial force of stent was dependant on various design parameters. The results show that amplitude was the dominant parameter in this study. Increasing either strut circumference or thickness generally improved radial force of stent. However, increasing either amplitude or radius of curvature generally weakened it. In conclusion, FEM can quantify the compressive mechanical property of stent and help designers to optimize stent systems.

The evolution of an ideal stent design and its impact on the aortic endothelium during and after percutaneous replacement.

Vascular support structures are important devices for treating valve stenosis. A large population of patients is treated for valvular disease and the preferred mode of treatment is percutaneous valve replacement. Stent devices are proving to be an improved technology in minimally invasive cardiac surgery. This new technology provides highly effective results at minimal cost and with a short duration of hospitalisation. Stents as a supporting structure for tissue valves have evolved over the years into remarkably useful and effective devices. During this process, a number of specific designs have come and gone, and a few have remained. Many design changes were successful, and many were not. This article describes the merits and demerits of various stent designs and details the specific reasons why a particular novel design is expected to be the most suitable implant during and after percutaneous aortic valve replacement.

Free radical scavenging activity from leaves of Acacia nilotica (L.) Wild. ex Delile, an Indian medicinal tree.

The present study compares the two extraction methods and evaluates the free radical scavenging activity of Acacia nilotica. Results indicated that the sequential extraction method was effective in concentrating the active principles in the ethanol extract as compared to the maceration method in DPPH assay. Based on the results, free radical scavenging property of the extracts obtained from sequential extraction method was analyzed in different assays to find out the possible antioxidant mechanism. Our results indicate that ethanol extract rich in phenolic and flavonoid contents had potent antioxidant activity and were significant in comparison with all the positive controls used in this study. The possible antioxidant mechanism of the ethanol extract can be due to its hydrogen or electron donating and direct free radical scavenging properties. Hence, the ethanol extract represents a source of potential antioxidants that could be used in pharmaceutical and food preparations.

Aqueous extract of Phyllanthus amarus inhibits chromium(VI)-induced toxicity in MDA-MB-435S cells.

Cr(VI) (hexavalent) is a very strong oxidant which causes high cytotoxicity through oxidative stress in tissue systems. Its abundance in groundwater and drinking water in several parts of the world has been noted to cause severe toxicity to both flora and fauna. This study evaluated the effects of aqueous extract of Phyllanthus amarus Schum. & Thon. against Cr(VI)-induced oxidative toxicity in vitro in MDA-MB-435S human breast carcinoma cells, along with an estimation of its antioxidant potential, inhibition of lipid peroxidation and determination of its polyphenolic composition. The extract showed significant (P<0.05) potential in scavenging free radicals (DPPH() and ABTS()(+)) and Fe(+3), and in inhibiting lipid peroxidation. A distinct decline in Cr(VI)-induced cytotoxicity was noticed in MDA-MB-435S cells with an increase in extract dosage. Furthermore, the extract proved to contain a high content of phenolic compounds which were found to have strong and significant (P<0.05) positive correlations to free-radical scavenging potential, lipid peroxidation inhibition capacity and cyto-protective efficiency against Cr(VI)-induced oxidative cellular damage. HPLC analysis identified some of the major phenolic compounds in it. It was concluded that P. amarus aqueous extract has high antioxidant potential (by virtue of its phenolic constituents) which simultaneously inhibits Cr(VI)-induced oxidative toxicity to MDA-MB-435S cells.

6-Shogaol inhibits monosodium urate crystal-induced inflammation--an in vivo and in vitro study.

Gout is a rheumatic disease that is manifestated by an intense inflammation secondary to monosodium urate crystal deposition in joints. In the present study, we assessed the effect of 6-shogaol (isolated active principle from ginger) on monosodium urate crystal-induced inflammation in mice; an experimental model for gouty arthritis and compared it with that of the non-steroidal anti-inflammatory drug, indomethacin. Paw volume and levels/activities of lysosomal enzymes, lipid peroxidation, anti-oxidant status and inflammatory mediator TNF-alpha were determined in control and monosodium urate crystal-induced mice. The levels of beta-glucuronidase and lactate dehydrogenase were also measured in monosodium urate crystal-incubated polymorphonuclear leucocytes (PMNL) in vitro. The levels of lysosomal enzymes, lipid peroxidation, and inflammatory mediator tumour necrosis factor-alpha and paw volume were increased significantly and the activities of anti-oxidant status were in turn decreased in monosodium urate crystal-induced mice, whereas these changes were reverted to near normal levels upon 6-shogaol administration. In vitro, 6-shogaol reduced the level of beta-glucuronidase and lactate dehydrogenase in monosodium urate crystal-incubated polymorphonuclear leucocytes in concentration dependent manner when compared to control cells. The present results clearly indicated that 6-shogaol exerted a strong anti-inflammatory effect and can be regarded as useful tool for the treatment of acute gouty arthritis.

Biomaterial optimization in a percutaneous aortic valve stent using finite element analysis.

BACKGROUND: Vascular support structures are important devices for treating valve stenosis. Large population of patients are treated for valvular disease and the principal mode of treatment is the use of percutaneous valvuloplasty. Stent devices are proving to be an improved technology in minimal invasive cardiac surgery. This technology now accounts for 20% of treatments in Europe. This new technology provides highly effective results at minimal cost and short duration of hospitalization. METHODS: This paper discusses the design and finite element analysis (FEA) of a percutaneous aortic valve stent. The stent design was modeled and subjected to FEA. The improved model design was carried out to meet the functional and surgical requirements. Analysis was done with different materials with loads ranging from 50 to 73 kgf/mm(2). These forces were selected because these values are far greater than the normal human blood pressure which ranges from 10 to 16 kPa. It was also to understand the mechanical behavior of different stent materials under such high pressures. RESULTS: A stent model was generated and its physical, mechanical, and behavioral properties were studied. Finite element analysis and simulation of the model help the designer to optimize the geometry suitable for performance during and after implantation. The design objective for the stent is to have long-term durability, low thrombogenicity, and resistance to migration and paravalvular leak. CONCLUSION: The analysis performed in this paper may aid in understanding the stent's tolerable pressure ranges in comparison with the physiological pressures exerted by the heart and cardiac blood flow during abnormal cardiovascular conditions. It may also help in finding the material that will best suit the stent.